rs865809

Variant names:

• chr3-184279947-A-G
• rs865809
• NM_001100121.2:c.816+1390A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100121.2(ECE2):​c.816+1390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 151,960 control chromosomes in the GnomAD database, including 50,826 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50826 hom., cov: 30)
• Consequence: ECE2 NM_001100121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 7 publications found

Genes affected

ECE2 (HGNC:13275): (endothelin converting enzyme 2) Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100121.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE2	NM_001100121.2	MANE Select	c.816+1390A>G		intron	N/A	NP_001093591.1	P0DPD6-2
	EEF1AKMT4-ECE2	NM_014693.4		c.1170+1390A>G		intron	N/A	NP_055508.3
	ECE2	NM_001100120.2		c.954+1390A>G		intron	N/A	NP_001093590.1	P0DPD6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE2	ENST00000404464.8	TSL:1 MANE Select	c.816+1390A>G		intron	N/A	ENSP00000385846.3	P0DPD6-2
	EEF1AKMT4-ECE2	ENST00000402825.7	TSL:1	c.1170+1390A>G		intron	N/A	ENSP00000384223.3	P0DPD8-1
	ECE2	ENST00000357474.9	TSL:1	c.954+1390A>G		intron	N/A	ENSP00000350066.5	P0DPD6-4

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123316 AN: 151842 Hom.: 50771 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.835

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.812 AC: 123419 AN: 151960 Hom.: 50826 Cov.: 30 AF XY: 0.804 AC XY: 59666 AN XY: 74252

African (AFR) AF: 0.947 AC: 39264 AN: 41480

American (AMR) AF: 0.828 AC: 12637 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2794 AN: 3472

East Asian (EAS) AF: 0.663 AC: 3419 AN: 5160

South Asian (SAS) AF: 0.640 AC: 3075 AN: 4806

European-Finnish (FIN) AF: 0.711 AC: 7490 AN: 10530

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52261 AN: 67938

Other (OTH) AF: 0.827 AC: 1744 AN: 2110

Alfa AF: 0.797 Hom.: 48567

Bravo AF: 0.831

Asia WGS AF: 0.673 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.45
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs865809; hg19: chr3-183997735;